Cell membrane potential: a signal to control intracellular pH and transepithelial hydrogen ion secretion in frog kidney.

The dependence of intracellular pH (pHi) and transepithelial H+ secretion on the cell membrane potential (Vm) was tested applying pH-sensitive and conventional microelectrodes in giant cells fused from single epithelial cells of the diluting segment and in intact tubules of the frog kidney. An increase of extracellular K+ concentration from 3 to 15 mmol/l decreased Vm from -49 +/- 4 to -29 +/- 1 mV while pHi increased from 7.44 +/- 0.04 to 7.61 +/- 0.06. Addition of 1 mmol/l Ba2+ depolarized Vm from -45 +/- 3 to -32 +/- 2 mV, paralleled by an increase of pHi from 7.46 +/- 0.04 to 7.58 +/- 0.03. Application of 0.05 mmol/l furosemide hyperpolarized Vm from -48 +/- 3 to -53 +/- 3 mV and decreased pHi from 7.47 +/- 0.05 to 7.42 +/- 0.05. In the intact diluting segment of the isolated-perfused frog kidney an increase of peritubular K+ concentration from 3 to 15 mmol/l increased the luminal pH from 7.23 +/- 0.08 to 7.41 +/- 0.08. Addition of Ba2+ to the peritubular perfusate also increased luminal pH from 7.35 +/- 0.07 to 7.46 +/- 0.07. Addition of furosemide decreased luminal pH from 7.32 +/- 0.03 to 7.24 +/- 0.05. We conclude: cell depolarization reduces the driving force for the rheogenic HCO3- exit step across the basolateral cell membrane. HCO3- accumulates in the cytoplasm and pHi increases. An alkaline pHi inactivates the luminal Na+/H+ exchanger. This diminishes transepithelial H+ secretion. Cell hyperpolarization leads to the opposite phenomenon. Thus, pHi serves as signal transducer between cell voltage and Na+/H+ exchange.